Pathomorphological analysis of budding in colorectal carcinomas

Authors

DOI:

https://doi.org/10.14739/2310-1237.2023.2.281722

Keywords:

colorectal carcinoma, immunohistochemistry, budding, cytokeratin

Abstract

Morbidity and mortality from colorectal cancer (CRC) remains a current problem of modern oncology. Intensive budding is an important prognostic factor for a worse clinical course of CRC and may influence clinical decision-making regarding the use of extended interventions in pT1 and stage II, according to the conclusion of the 2016 International Consensus Conference on Tumor Budding.

The aim of the work is to evaluate the prognostic significance of budding depending on the clinical and morphological characteristics of colorectal carcinomas.

Materials and methods. The article deals with clinical and anatomical material of 31 patients with CRC (14 women and 17 men) who were treated in the 2nd surgical department of the SE “Dnipropetrovsk Regional Clinical Hospital” in the period from 2019 to 2021. The age of the patients varied of 27–84 years old (average age – 62.3 ± 14.8 years old). A histological examination of CRC samples was carried out with an assessment of “hot areas” of the invasive front and an immunohistochemical examination with РАН CK АЕ 1/3, Ki-67, MUC2, caspase-3, β-catenin to calculate the number of tumor cell clusters.

Results. In one third of the number of samples, differences were determined not only in the number of clusters, but also in the budding category when stained by routine and immunohistochemical methods. Peritumoral budding of the invasive front with category Bd3 was always accompanied by intratumoral budding of varying degrees of intensity. The analysis of the distribution of gradations of budding of colorectal carcinomas by gender, age, location, histological degree of differentiation, and the presence of metastases did not show a statistically significant difference (p > 0.05), which may indicate the independence of this factor on the prognosis of patient survival. The intensity of budding of colorectal carcinomas depending on the expression of markers Ki-67, caspase-3 and β-catenin did not show a significant difference in subgroups (p > 0.05) but showed tendencies to increase the number of budding with an increase in the proliferation index and a decrease in the activity of the proapoptotic enzyme caspase-3.

Conclusions. If the number of buds on the border of categories Bd1 and Bd2, or Bd2 and Bd3, determined by the standardized method of H & E staining is doubtful, the degree of budding may be underestimated in comparison with staining by the immunohistochemical method, due to the exclusion of falsely interpreted morphological objects as tumor clusters; the most reliable immunohistochemical marker for contrast separation of buds is a cocktail of cytokeratins.

Author Biographies

I. S. Shponka, Dnipro State Medical University, Ukraine

MD, PhD, DSc, Professor, First Vice-Rector of Dnipro State Medical University, Ukraine

O. V. Poslavska, Dnipro State Medical University, Ukraine

MD, PhD, DSc, Аssociate Professor, Acting Head of the Department of Pathological Anatomy, Forensic Medicine and Pathological Physiology

I. K. Kharkhalis, Uzhhorod National University, Ukraine

MD, Assistant of the Department of Skin and Venereal Diseases

T. V. Shynkarenko, Dnipro State Medical University, Ukraine

MD, PhD, Аssociate Professor of the Department of Pathological Anatomy, Forensic Medicine and Pathological Physiology

References

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660

Qu, Q., Wu, D., Li, Z., & Yin, H. (2023). Tumor budding and the prognosis of patients with metastatic colorectal cancer: a meta-analysis. International journal of colorectal disease, 38(1), 141. https://doi.org/10.1007/s00384-023-04423-8

Lugli, A., Zlobec, I., Berger, M. D., Kirsch, R., & Nagtegaal, I. D. (2021). Tumour budding in solid cancers. Nature reviews. Clinical oncology, 18(2), 101-115. https://doi.org/10.1038/s41571-020-0422-y

Ulase, D., Heckl, S., Behrens, H. M., Krüger, S., & Röcken, C. (2020). Prognostic significance of tumour budding assessed in gastric carcinoma according to the criteria of the International Tumour Budding Consensus Conference. Histopathology, 76(3), 433-446. https://doi.org/10.1111/his.13997

Lugli, A., Kirsch, R., Ajioka, Y., Bosman, F., Cathomas, G., Dawson, H., El Zimaity, H., Fléjou, J. F., Hansen, T. P., Hartmann, A., Kakar, S., Langner, C., Nagtegaal, I., Puppa, G., Riddell, R., Ristimäki, A., Sheahan, K., Smyrk, T., Sugihara, K., Terris, B., … Quirke, P. (2017). Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Modern pathology, 30(9), 1299-1311. https://doi.org/10.1038/modpathol.2017.46

Baidoun, F., Elshiwy, K., Elkeraie, Y., Merjaneh, Z., Khoudari, G., Sarmini, M. T., Gad, M., Al-Husseini, M., & Saad, A. (2021). Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes. Current drug targets, 22(9), 998-1009. https://doi.org/10.2174/1389450121999201117115717

Chhikara, B. S., & Parang, K. (2023). Global Cancer Statistics 2022: the trends projection analysis. Chemical Biology Letters, 10(1), 451-451.

Mitrovic, B., Handley, K., Assarzadegan, N., Chang, H. L., Dawson, H. A. E., Grin, A., Hutchins, G. G. A., Magill, L., Quirke, P., Riddell, R. H., Gray, R. G., Kirsch, R., & QUASAR Collaborative Group (2021). Prognostic and Predictive Value of Tumor Budding in Colorectal Cancer. Clinical colorectal cancer, 20(3), 256-264. https://doi.org/10.1016/j.clcc.2021.05.003

Fedorenko, Z. P., Hulak, L. O., Mykhailovych, Yu. Y., Horokh, Ye. L., Ryzhov, A. Yu., Sumkina, O. V., & Kutsenko, L. B. (2021). Rak v Ukraini, 2019-2020. Zakhvoriuvanist, smertnist, pokaznyky diialnosti onkolohichnoi sluzhby [Cancer in Ukraine, 2019-2020. Morbidity, mortality, performance indicators of the oncology service]. Bulletin of the National Chancery Register of Ukraine, 22. [in Ukrainian]. http://www.ncru.inf.ua/publications/BULL_22/

Marx, A. H., Mickler, C., Sauter, G., Simon, R., Terracciano, L. M., Izbicki, J. R., & Clauditz, T. S. (2020). High-grade intratumoral tumor budding is a predictor for lymphovascular invasion and adverse outcome in stage II colorectal cancer. International journal of colorectal disease, 35(2), 259-268. https://doi.org/10.1007/s00384-019-03478-w

Zlobec, I., & Lugli, A. (2018). Tumour budding in colorectal cancer: molecular rationale for clinical translation. Nature reviews. Cancer, 18(4), 203-204. https://doi.org/10.1038/nrc.2018.1

Vareniuk I. M., & Dzerzhynskyi M. E. (2019). Metody tsyto-histolohichnoi diahnostyky [Methods of cyto-histological diagnosis]. Kyiv: Interservis. [in Ukrainian].

Nguyen, T. (2022). Immunohistochemistry: A Technical Guide to Current Practices. Cambridge: Cambridge University Press.

Melling, N., Kowitz, C. M., Simon, R., Bokemeyer, C., Terracciano, L., Sauter, G., Izbicki, J. R., & Marx, A. H. (2016). High Ki67 expression is an independent good prognostic marker in colorectal cancer. Journal of clinical pathology, 69(3), 209-214. https://doi.org/10.1136/jclinpath-2015-202985

Shams, T. M., Atwa, M. M., & Shams, M. E. (2012). Negative correlation between caspase-3 and COX-2 expression in colon cancer. Egyptian Journal of Pathology, 32(1), 68-74. https://doi.org/10.1097/01.xej.0000417555.65230.8d

Kazem, A., Sayed, K. E., & Kerm, Y. E. (2014). Prognostic significance of COX-2 and β-catenin in colorectal carcinoma. Alexandria journal of medicine, 50(3), 211-220. https://doi.org/10.1016/j.ajme.2013.05.007

Poslavska, O. V. (2015). Metodolohiia vykorystannia prohramnoho zabezpechennia dlia analizu tsyfrovykh mikrofotohrafii na bazi kursu patomorfolohii z metoiu pidvyshchennia profesiinoho rivnia studentiv i naukovtsiv [The methodology of using software for the analysis of digital photomicrographs based on the course of pathomorphology in order to improve the professional level of students and scientists]. Morphologia, 9(3), 122-126. [in Ukrainian].

Strakhova, O. P., & Androsov, O. I. (2021). Statystychni metody opratsiuvannia rezultativ medyko-biolohichnykh doslidzhen [Statistical methods of processing the results of medical and biological research]. Lviv: Karavela. [in Ukrainian].

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Published

2023-08-30

How to Cite

1.
Shponka IS, Poslavska OV, Kharkhalis IK, Shynkarenko TV. Pathomorphological analysis of budding in colorectal carcinomas. Pathologia [Internet]. 2023Aug.30 [cited 2024Nov.24];20(2):135-40. Available from: http://pat.zsmu.edu.ua/article/view/281722

Issue

Vol. 20 No. 2 (2023): Pathologia

Section

Original research

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